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Publication : JMJD3 activated hyaluronan synthesis drives muscle regeneration in an inflammatory environment.

First Author  Nakka K Year  2022
Journal  Science Volume  377
Issue  6606 Pages  666-669
PubMed ID  35926054 Mgi Jnum  J:328273
Mgi Id  MGI:7328662 Doi  10.1126/science.abm9735
Citation  Nakka K, et al. (2022) JMJD3 activated hyaluronan synthesis drives muscle regeneration in an inflammatory environment. Science 377(6606):666-669
abstractText  Muscle stem cells (MuSCs) reside in a specialized niche that ensures their regenerative capacity. Although we know that innate immune cells infiltrate the niche in response to injury, it remains unclear how MuSCs adapt to this altered environment for initiating repair. Here, we demonstrate that inflammatory cytokine signaling from the regenerative niche impairs the ability of quiescent MuSCs to reenter the cell cycle. The histone H3 lysine 27 (H3K27) demethylase JMJD3, but not UTX, allowed MuSCs to overcome inhibitory inflammation signaling by removing trimethylated H3K27 (H3K27me3) marks at the Has2 locus to initiate production of hyaluronic acid, which in turn established an extracellular matrix competent for integrating signals that direct MuSCs to exit quiescence. Thus, JMJD3-driven hyaluronic acid synthesis plays a proregenerative role that allows MuSC adaptation to inflammation and the initiation of muscle repair.
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